Model of radiation-induced ambulatory dysfunction

Peter Belafsky, Shannon Clayton, Joehleen Archard, Jordan Pavlic, Shyam Rao, D. Farwell, Maggie Kuhn, Peter Deng, Julian Halmai, Gerhard Bauer, Kyle Fink, Brian Fury, Nicholas Perotti, Jon Walker, Angela Beliveau, Andrew Birkeland, Marianne Abouyared, Whitney Cary, Jan Nolta, Johnathon Anderson

Research output: Contribution to journalArticlepeer-review

Abstract

Approximately 50% of oncology patients receive radiotherapy, with the dose of radiation often being limited to mitigate normal tissue damage of proximal critical/sensitive structures. Currently, no preclinical models exist to study a putative drug's efficacy in terms of functional recovery of tissues adversely effected by radiation exposure. Such limitations inhibit the development of targeted therapeutics. To this end, we developed a model of radiation-induced soft-tissue damage with quantitative outcomes of tissue function. Mice received a single administration of radiation focused on the posterior limb while under anesthesia. A blinded observer weighed each mouse and performed motors skills assessments weekly for the duration of the study. At the end of the study, mice were euthanized, assessed for hindlimb range of motion and histological analysis was performed, evaluating tissue morphology and fibrotic scarring. Mice presented numerous significant ambulatory deficits that positively correlated with the dose of radiation administered. Irradiated mice presented with reduced range of motion and increased fibrotic scarring upon histological assessment across all dose groups as compared to controls. The current study is the first to describe a preclinical model of functional skeletal muscle deficits following focal radiation injury of a posterior limb, which will be useful for the assessment of novel drug candidates to treat radiotherapy-induced soft-tissue damage.

Original languageEnglish (US)
Pages (from-to)201-210
Number of pages10
JournalJournal of Medical Sciences (Taiwan)
Volume41
Issue number4
DOIs
StatePublished - Jul 1 2021

Keywords

  • collagen
  • fibrosis
  • motor skills
  • muscle
  • radiation
  • Radiation

ASJC Scopus subject areas

  • Medicine(all)

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